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BACKGROUND: Fractional exhaled nitric oxide (FENO) has emerged as a biomarker of type-2 (T2) airway inflammation (AI), primarily reflecting IL-13 activity. Reducing airway calibre reduces FENO levels, suggesting an impact of airway obstruction.

OBJECTIVE: This study compared the relative contributions of airway IL-13 and airway calibre to FENO values in asthma patients. We also investigated how airway calibre reduction affects FENO thresholds for detecting active T2 airway inflammation.

METHODS: FENO and FEV₁ measurements as well as sputum induction were performed in 120 asthma patients and 13 controls. Elevated sputum IL-13, IL-5 or eosinophils identified 100 patients with active T2 airway inflammation. The contributions of IL-13 and FEV₁ to FENO were assessed in asthmatics with clear evidence of T2 airway inflammation by multivariable linear models. ROC curve analysis was used to identify FENO thresholds marking the presence of active T2 airway inflammation according to FEV₁.

RESULTS: In type-2 patients, IL-13 and FEV₁ contribute significantly (p=0.005 and p=0.008, respectively) to FENO based on multivariable analysis. From the ROC curve analysis, the FENO threshold corresponding to a specificity >85% was 45 ppb in the whole population. and dropped to 22 ppb in patients with FEV₁<70%.

CONCLUSION: Airway calibre is a major determinant of FENO values in asthma, as crucial as concomitant T2 airway inflammation. As a result, the optimal thresholds for FENO to signal the presence of active T2 airway inflammation in asthmatics decrease significantly as FEV₁ decreases. New thresholds considering the impact of lung function should be established in larger cohorts.